title: Phenotype and regulation of immunosuppressive Vδ2-expressing γδ T cells.
abstract: The proliferation and interleukin-2 production of CD4(+)CD25(-) αβ T cells were inhibited in a cell-contact manner by Vδ2 γδ T cells. The transcription factor Helios was constitutively expressed in about one-third of circulating γδ T cells and was upregulated by CD28-signaling. Our data suggest that Helios could serve as a marker for differential activation status rather than for regulatory T cells (Treg). Our findings also indicate that the interaction of CD86 on activated Vδ2 T cells and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) on activated αβ T cells mediated the suppression because the suppressive effect was abolished by blocking the CD86:CTLA-4 interaction. Pre-treatment of Vδ2 T cells with Toll-like receptor 2 ligands enhanced phosphorylation of MAPKs, Akt, and NF-κB and partially abrogated the suppressive capacity, whereas on co-cultured responder T cells inhibitory molecules were downregulated and Akt and NF-κB phosphorylation was restored. Our results suggest that the regulation of αβ T cell proliferation by activated Vδ2 T cells might contribute to fine-tuning of αβ T cell responses.
authors.affiliation: Institute of Immunology, Christian-Albrechts University of Kiel, Arnold-Heller Strasse 3, Haus 17, 24105, Kiel, Germany, Christian.Peters@uksh.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Peters
authors.forename: Hans-Heinrich
authors.initials: HH
authors.lastname: Oberg
authors.forename: Dieter
authors.initials: D
authors.lastname: Kabelitz
authors.forename: Daniela
authors.initials: D
authors.lastname: Wesch
mesh_terms: D051940:B7-2 Antigen / Q000378:metabolism; D060908:CTLA-4 Antigen / Q000378:metabolism; D002478:Cells, Cultured; D018920:Coculture Techniques; D004075:Diglycerides / Q000494:pharmacology; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007165:Immunosuppression Therapy; D055666:Lipopeptides / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology; D010641:Phenotype; D010766:Phosphorylation; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D051195:Toll-Like Receptor 2 / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D051940:B7-2 Antigen; D060908:CTLA-4 Antigen; D004075:Diglycerides; C418974:FOXP3 protein, human; C460864:FSL-1 lipoprotein, synthetic; D051858:Forkhead Transcription Factors; D055666:Lipopeptides; D009842:Oligopeptides; D016692:Receptors, Antigen, T-Cell, gamma-delta; D051195:Toll-Like Receptor 2; D020928:Mitogen-Activated Protein Kinases